The molecular biology of tumor metastasis has been investigated. A cDNA clone, pNM23, has been identified which recognizes specific RNAs present to a greater degree in low metastatic K1735 murine melanoma cell lines than in related, highly metastatic K1735 melanoma cell lines. The pNM23 cDNA clone has been tested in three additional animal experimental metastases systems: rat nitrosomethylurea-induced mammary carcinomas, murine mammary tumor virus-induced mammary carcinomas and rat embryo fibroblasts transfected with ras + adenovirus Ela. In each case, NM23 RNA levels were inversely correlated with metastatic potential. Preliminary experiments suggest that NM23 RNA levels are also differentially expressed in human breast cancer. Approximately 750 bp of the NM23 gene have been isolated and are being characterized, with the eventual goal of transfecting the full length NM23 gene into highly metastatic cells. Computer analysis of the 3' 600 bp of the NM23 cDNA indicate that it is a novel gene. The data identify a new gene which is associated with the metastatic process. Further, the NM23 gene demonstrates that tumor metastasis is not only associated with the acquisition of invasive and other traits, but may also involve the loss of other cellular functions. Experiments underway will determine the diagnostic and therapeutic potential of this finding.